Suppressed Plasma Angiotensin II and Reduced Antioxidant Enzyme Expression Contribute to Impaired Vascular Relaxation in Dahl Salt‐Sensitive Rats

Abstract

Dahl salt‐sensitive (SS) rats exhibit impaired regulation of the renin gene and chronically low plasma angiotensin II (ANG II) levels. Normal ANG II levels and impaired vasodilator responses are restored when chromosome 13 (chr13) from the Brown Norway (BN) rat is introgressed onto the SS genetic background. This study used novel congenic rats [SS.BN‐(D13hmgc41‐D13hmgc23)] containing a 2.0 Mbp portion of chr13 including the BN renin allele to investigate the role of ANG II levels in maintaining vasodilator responses and antioxidant enzyme expression. Male SS and congenic (Ren1‐BN) rats (10‐14 weeks old) were fed a low‐salt diet (0.4% NaCl) after weaning. Responses of isolated middle cerebral arteries (MCA) to acetylcholine (ACh; 10−10 ‐ 10−5 M), reduced PO2 (perfusion and superfusion solution PO2 ≈35‐45 mmHg) and sodium nitroprusside (SNP; 10−12 ‐ 10−4 M) were assessed via video microscopy. MCA from the Ren1‐BN congenic rats dilated in response to ACh and reduced PO2 while MCA from the SS rats did not. Both strains exhibited a dose‐dependent dilation to the NO donor SNP. Cu/Zn SOD expression was significantly reduced in arteries from SS rats vs. Ren1‐BN rats. These results suggest that introduction of a normally functioning renin gene into the SS genetic background restores normal vasodilator responses by increasing antioxidant enzyme expression and reducing vascular oxidative stress. (NIH #HL65289, #HL72920).